AbstractTreatment of medial compartment knee osteoarthritis with high tibial osteotomy can produce an unintended change in the slope of the tibial plateau in the sagittal plane. The effect of changing posterior tibial slope (PTS) on cruciate ligament forces has not been quantified for knee loading in activities of daily living. The purpose of this study was to determine how changes in PTS affect tibial shear force, anterior tibial translation (ATT), and knee‐ligament loading during daily physical activity. We hypothesized that tibial shear force, ATT, and ACL force all increase as PTS increases. A previously validated computer model was used to calculate ATT, tibial shear force, and cruciate‐ligament forces for the normal knee during three common load‐bearing tasks: standing, squatting, and walking. The model calculations were repeated with PTS altered in 1° increments up to a maximum change in tibial slope of 10°. Tibial shear force and ATT increased as PTS was increased. For standing and walking, ACL force increased as tibial slope was increased; for squatting, PCL force decreased as tibial slope was increased. The effect of changing PTS on ACL force was greatest for walking. The true effect of changing tibial slope on knee‐joint biomechanics may only be evident under physiologic loading conditions which include muscle forces. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29:223–231, 2011